Ammonia → HCID 59371494, compound

Participants

Reaction Steps

In a 100 mL round-bottom flask, a mixture of trifluoroacetic acid (1.2 mL) and water (0.12 mL) was added to a solution of tert-butyl 3-[5-[[1-(benzyloxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]benzylcarbamate (329 mg, 653 μmol) in CH2Cl2 (6 mL). The flask was loosely stoppered, and the mixture was stirred magnetically for 7 h. Shortly before, a small aliquot was worked up with aq. NaHCO3/EtOAc and analyzed by TLC (UV detection; SiO2, EtOAc: Rf 0; SiO2, CH2Cl2/MeOH/conc. aq. NH3 87:13:3: Rf approx. 0.55), indicating complete conversion of the starting material. The mixture was evaporated (40° C./14 torr) to obtain a colorless glass (0.76 g), which was taken up in MeOH (3 mL). The pH was adjusted to approx. 8-9 (indicator paper) by adding a few drops of conc. NH3, and the solution was evaporated again. The residue was chromatographed on SiO2 (20×1.9 cm, CH2Cl2/MeOH/conc. aq. NH3 87:13:3), and the product-containing fractions were evaporated and dried (40° C./oil pump) to obtain 262 mg (99.5%) of the free primary amine as a slightly yellowish glass. 1H NMR (CDCl3, 500 MHz) δ 8.50 (s, 1H), 8.32 (br, 1H), 7.56 (s, 1H), 7.51-7.45 (m, 2H), approx. 7.43 (br and overlapping, 1H), 7.40 (m, 1H), 7.32 (br s, 5H), 5.13, 5.08 (ABq, 2H, J=12.3 Hz), 4.67 (m, 1H), approx. 4.5 (br, 1H), 4.22 (br s, 1H), 4.09-4.00 (m, 2H), 3.99 (s, 2H), 2.51-2.37 (m, 2H), 1.64 (br, NH2 and H2O). MS (EI) m/z 403 (M+, 5.8%), 312 (6.4%), 200 (5.4%), 199 (4.0%), 91 (100%).

Provenance & Evidence